Quickshot: Evaluation of Varicose Vein-derived Blood Biomarkers for Venous Surveillance

Objective: Intervention for patients with symptomatic varicose veins is largely driven by a combination of symptoms, the magnitude of venous reflux, clinical severity scoring algorithms, and unresponsiveness to medical therapy. We evaluated the wall of superficial veins from patients with symptomatic varicose veins, comparing this to healthy veins, for biological insight into progression of superficial vein disease.

Methods: RNA was extracted from incompetent greater saphenous vein (GSV) at the time of phlebectomy and compared to residual healthy superficial veins following coronary artery bypass graft surgery. The venous transcriptome was interrogated by Nanostring ®. Panther and Gene Ontology identified biological pathways of interest and, based on this data, plasma biomarkers form varicose vein patients or matched controls was evaluated by ELISA. The relationship between target blood biomarker concentration and venous reflux time was then assessed.

Results: Multiple genes were unregulated and down regulated (Fig. 1) in pathways involving angiogenesis, collagen biosynthesis, and inflammation.  COL10A1 and COL1A1 were unregulated in varicose vein by 12-fold and 5-fold, respectively, while interleukin-6 (IL-6 was downregulated by > 30-fold.  Blood [IL-6] was higher in the blood of varicose vein vs. healthy vein patients (4.8 vs. 1.3 pg/mL, P=0.0085) and distinguished varicose vein patients from healthy vein individuals by ROC curve analysis with area under the curve (AUC)=70% (57-83), P=0.009).  Blood collagen 1A1 (Col-1A1) was lower in the blood of varicose vein patients vs. healthy patients (66355 vs. 82661 pg/mL, P=0.04).  Only blood [Col1A1] was related to reflux times with an inverse correlation (r= -0.51, P=0.0098) (Fig. 2).

Conclusions: Blood [Collagen 1A1] and possibly Interleukin-6 may be blood biomarkers used in conjunction with venous reflux times as additional objective data that that may indicate adverse remodeling of the vein, and assist in decision-making for interventional therapy.